There are several types of photometric devices used in a variety of different applications. In general, photometric devices include devices that are used to measure or otherwise determine one or more characteristics of light, such as intensity, color, wavelength, or other characteristic.
One type of photometric device is an optical absorbance probe, which is used in the biotechnology, chemical, brewery, pulp and paper, fermentation, pharmaceutical, winery, and other sectors of industry and/or research. With biotech applications, one type of optical absorbance probe known as “cell density probes” are ordinarily used to monitor cell growth in a cell culture. In a typical implementation, live cells and some type of suitable growth agent (as well as possibly other additives) are placed in a vat or other vessel, with the growth agent, cells, and possibly other additives together forming a “broth” made up of liquid and suspended particulates (e.g., the cells). Conditions in the vat are then appropriately controlled to induce the cells to multiply and grow. The cells, once a sufficient amount have been grown, are harvested for various uses.
Cell density probes are used to monitor the cell growth in the vat at various times during the growing cycle, so as to ensure that the cells are growing at a proper rate and/or to verify whether a sufficient number of cells have been grown. Use of a cell density probe is an alternative to manual cell counting techniques, wherein cells in a sample from the vat are extracted and physically counted (and thus result in a high degree of error and is very labor intensive). In comparison, a density probe allows the number of cells to be automatically determined by correlation of light absorbance to cell density (e.g., the determined cell density can be correlated to the number of cells and/or cell growth rate in the broth).
A typical cell density probe includes a tip that has an optical gap. The cell density probe is immersed into the vat, such that the optical gap and tip are completely covered in the broth. A light is transmitted from a first end of the optical gap to second end of the optical gap. As the light passes through the optical gap, the cells present within the optical gap absorb a certain amount of the light. Therefore, the light received at the second end of the optical gap will have a lower intensity than the light transmitted from the first end of the optical gap, due to the absorbance of the light by the cells, which is typically expressed in terms of absorbance units (A.U.). The intensity of the received light decreases as the density of cells increase. Persons skilled in the art can correlate various intensities of the received light with growth rates and cell densities for the particular cell type that is involved. Accordingly, by monitoring the intensity of the received light over a period of time, the user of the cell density probe can determine if the growth rate is proceeding normally, if a sufficient number of cells have been grown, and/or whether a problem has occurred in the growing cycle. For example, if the cell density probe provides a light intensity measurement that is higher than expected for that particular time in the growth cycle, then the high intensity measurement may be indicative of contamination or other environmental condition that is impeding the capability of the cells to grow properly.
In the biotech industry, particular importance is placed on clinical trials. Accordingly, it is in the best interest of companies seeking Federal Drug Administration (FDA) approval, for instance, to be able to readily provide documentation and other evidence that their equipment was calibrated and functioning properly, accurate measurements were taken, and other information to validate results. Of course, proper calibration of equipment (such as cell density probes) outside of the clinical trial environment is also desirable from a day-to-day operation point of view, whether for the biotech industry or for other industry or research involving the monitoring of cell growth cycles.
However, existing techniques to calibrate or otherwise verify the proper operational state of a cell density probe are impractical, insufficient, and prone to error. For instance, one technique for calibration is to first take the cell density probe offline, which involves removal of the cell density probe from the vat for calibration or calibration of the cell density probe prior to immersion in the vat. A neutral density filter, whose absorption (in A.U.) is known precisely, is then slid into or otherwise placed within the optical gap of the cell density probe's tip. The cell density probe is then activated such that light is transmitted from the first end of the optical gap and through the neutral density filter therein. Since the intensity of the transmitted light and the absorption of neutral density filter are both known quantities, the intensity of the light received at the second end of the optical gap should be consistent with the known quantities. For example, a neutral density filter having 1 A.U. corresponds to 90.00% absorbance. Thus, if there is a 10.00% detected intensity in the received light, as compared to the transmitted light, then the cell density probe is operating properly. For added verification, several neutral density filters, each having different grades of absorbance, can be sequentially placed in the optical gap to verify other detected intensity values. A higher-than-expected or a lower-than-expected detected intensity can be indicative of a malfunction in the cell density probe's electronics.
There are several disadvantages of using the above-described calibration technique. One disadvantage is that the cell density probe needs to be physically removed from the vat in order to perform the testing and calibration. This removal thus involves and requires physical user intervention, and further disturbs the operation of the device. Moreover, the testing and calibration is being performed offline out of the vat while the cell density probe's tip is not immersed in the broth, and therefore may not necessarily produce results that are representative of actual conditions in the vat.